Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are nuclear medicine techniques that enable the study of neurotransmitter receptors in living animals and humans, but the lack of suitable radiotracers for some neurotransmitter systems has limited the usefulness of these techniques. In the past year, a series of halogenated derivatives of A-85380 [-3-(2(S)-azetidinylmethoxy)pyridine] were synthesized and three compounds with exceptional promise as radiotracers for nicotinic acetylcholine receptors (nAChRs) were identified. The 5-iodo-, 5-bromo- and the 2- and 6-fluoro analogs of A-85380, rapidly entered the brain, bound tightly and selectively to the subtype of nAChRs that predominates in the brain and is linked to the dopamine reward system. Further, these compounds are orders of magnitude safer than currently used radiotracers or new tracers derived from epibatidine. The synthesis of radiolabeled 5-[I-123/125] and 2- and 6-[F-18] A-85380 yielded tracers with high specific activities. A series of nonhuman primate studies demonstrated that the new radiotracers can image nAChRs using either PET or SPECT imaging techniques without producing observable biological effects. These new nAChRs will be beneficial for studying mechanisms of tobacco dependence and neurodegenerative diseases. Another goal has been to improve our quantitative analysis of PET data for assaying receptor-ligand binding. Using modeling techniques incorporating analyses of both experimental [C-11]-raclopride PET data as well as computer-simulated data, we developed a simple procedure for correction of the artifact due to partial volume error. The unwanted correlation of binding potential estimates with structure size can be eliminated by using a technique requiring only measurements of structure size and foreground to background contrast on the brain images.